Method for removal of a side chain



METHOD FOR REMOVAL OF A SIDE CHAIN I Lloyd B. Barkley, Brentwood, M0.,assignor to Monsanto Chemical Company, St. Louis, Mo., a corporation ofDelaware No Drawing. Application November 15, 1254, Serial No. 468,999

6 Claims. (Cl. 260-586) This invention relates to a process for removalof the ,B-carboxyethyl side chain of certain polyhydrophenam threnecompounds referred to hereinafter as keto-acids.

1,8a dimethyl Alma) polyhydrophenanthren 2 ones of the structure where Ris a substituted or unsubstituted 4-carbon atom chain forming a6-membered fused ring as described, are

employed in the total synthesis of steroidal compoundsof thecyclopentanopolyhydrophenanthrene series. In the intermediary stepswhich provide for ring A a B-carboxy-i ethyl group is introduced to the1-position of said 1,8a-. dimethyl A polyhydrophenanthren 2 ones. By sodoing a new asymmetric center is introduced which.

yields therefore a one hundred percent increase in' the number ofgeometric isomers.

where R is a 4-carbon atom chain, which 4-carbon atom chain forms a6-membered fused ring as described, is conveniently and eflicientlyremoved by a process comprising continuously adding the keto-acid to amelt of an alkali metal salt of a hydrocarbon carboxylic acid atapproximately the rate at which the keto-acids side chain is pyrolyzed,the 1,821 dimethyl Alum) polyhydrophenanthren 2 one being recovered bydistillation from the molten mass as it forms.

In the process of this invention the pyrolyzing temperature will be notlower than that at which the 1,8a-dimethyl- Amen) polyhydrophenanthren 2one distills from the molten mass but less than its decompositiontemperature. Although any pressure below atmospheric is operable, it ispreferred that pressures below 100 mm. of mercury be employed.

These isomers are gen-. erically termed keto-acids, half of which aretermed Otnited States ice.

2 j The free keto-acids are prepared by methods fully de-' scribed inthe literature, e. g. I. A. C. S., 74, pp. 422317.

1,8a dimethyl 1 ,61 carboxyethyl) A deca hydrophenanthren 2 one;

1,8a dimethyl 1 (,8 carboxyethyl) A hydrophenanthren 2 one;

1,8a dimethyl 1 (,8 carboxyethyl) A -.dodeca hydrophenanthren 2,8 dione;

1,8a dimethyl 1 (,8 carboxyethyl) 8 A dodecahydrophenanthren 2 one;

1,8a dimethyl l (,8 carboxyethyl) 8 chloro A dodecahydrophenanthren 2one;

1,8a dimethyl 1 (B carboxye thyl) 6,7 dihy droxy Adodecahydrophenanthren 2 one acetonide; and like 1,8a dimethyl 1 (Bcarboxyethyl) A polyhydrophenanthren 2 ones.

As illustrative of the process of this invention is the following: I

, Example I To a suitable reaction vessel equipped with a take off" tubeconnected through a vacuum adapter to areceiving vessel containing amolten mass consisting of 50 parts by weight of sodium acetate and 50parts by weight of po tassium acetate is added approximately 50 parts byweight of the a isomer of I anti trans 41,8a dimethyl;- 1(B-carboxyethyl) A decahydrophenanthren 2 one. The addition is made overa period of about one hour while maintaining the temperature at 280300under 2 mm. of mercury vacuum, the l anti trans 1,8a dimethyl 13decahydrophenanthrene 2 one distilling off as it forms. The amount of l-.anti trans 1,8a dimethyl A decahydrophenanthren 2 one (a colorlesscrystalline solid, M. P. 42-44 C.) recovered is 20 parts by weight.

dium phenacetate instead. of the mixture of acetates similar results areobtained.

Colorless oily dl anti trans 1,821 dimeth l-M decahydrophenanthren 2 oneis obtained employing the procedure of Example I using either thea-isomer or the ,8 isomer of a! anti trans 1,8a dimethyl 1 (Bcarboxyethyl) A6110 decahydrophenanthren 2 one instead of the oc isomerof l anti trans 1,8a dimethyl 1 ([3 carboxyethyl) A decahydrophenanthren2 one.

Employing the procedure of Example I but replacing the a isomer of lanti trans 1,8a dimethyl A decahydrophenanthren 2 one with a chemicallyequivalent amount of the 13 isomer of a'l anti trans 1,8a dimethyl 1 (5carboxyethyl) 6,7 dihydroxy A dodecahydrophenanthren 2 one acetonide andthe mixture of alkali metal acetates with an equal weight of sodiumbenzoate white crystalline dl anti trans 1,8a dimethyl 6,7 dihydroxyAmen) dodecahydrophenanthren 2 one acetonide is obtained.

The amount of alkali metal salt of a hydrocarbon monocarboxylic acid towhich the keto-acid is continuously added may vary widely, however, itis preferred that the addition he so controlled that from 0.5 to 20parts by weight for each part by weight of the keto-acid be present. Ingeneral, however, 1 to 5 parts by Weight for each part by weight of theketo-acid gives optimum results.

The alkali metal salts of hydrocarbon carboxylic acids contemplated bythis invention are those of the general formula R'C0.0M, where R is analkali metal such as Na, K or Li and where R is a hydrocarbon radicalsuch as methyl, ethyl, propyl, butyl, amyl, hexyl, octyl, decyl, benzyl,phenethyl, phenpropyl, phenyl, tolyl, ethylphenyl,

Patented June 5, I956;

dodecabromo naphthyh etc. It, is. preterred that R contain not more than10 carbon atoms. As specifically illustrative of the carboxylic acidsalts contemplated are sodium acetate, potassium acetate, sodiumpropionate, sodium butyrate, so-

eapreate, sqdium Qaprylate, sodium phenylacetate, sodium benzoate,sodium naphthoate, and the like and umiflals.v mixtures. thereof. The;sodium salts of the 10w molecular weight aliphatic monocarboxylic acidsare preterred.

While the present invention has been described with respect to several.embodiments it is to be understood it is not so limited and thatvarious, modifications thereof may be mad W hin. the skill of thoseversed. in the art without departing from the spirit or scope. of theinvert.- iou.

What is claimed is:

1,. The process, 01: remouingaflrcarboxyethyl side chain from aketo-acid of. the structure where R is a 4-carbon atom chain which formsa 6-membered fused ring as described, which comprises continuouslyadding: the keto-acid to a melt of an alkali metal where R. has thsignificance.- aforedescribed, by distillation from the molten mass. as.it terms, the. pressure during. the pyrolysis being below atmospheric.

2. The process of claim I wherein the pressure is below 100 mm. ofmercury.

3. The process of claim 1 wherein the alkali metal salt of a hydrocarbonmonocarboxylic acid is the sodium salt of a low molecular weightaliphatic carboxylic acid.

4. The process of removing the fl-carboxyethyl side chain from an antitrans 1',8a dimethyl 1 (13 car boxyethyl) A decahydrophenanthren 2 oneof the structure.

which comprises continuously adding the keto acid to a melt of analkali. metal salt. of a. hydrocarbon monocarboxylic. acid. atapproximately the rate at which the ketozacids side chain ispyrolyzedand recovening. an anti-trans- 1,8a dimethyl A decahydrophenanthren 2oneof the structure CH: l

No. references cited.

1. THE PROCESS OF REMOVING A B-CARBOXYETHYL SIDE CHAIN FROM A KETO-ACIDOF THE STRUCTURE